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Multiple myeloma with extramedullary disease: impact of autologous stem cell transplantation on outcome

Bone Marrow Transplantation volume 52, pages 1473–1475 (2017)Cite this article

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Survival of patients with multiple myeloma (MM) has improved significantly during the past 15 years. This has been attributed to use of novel agents (for example, immune modulators, proteasome inhibitors) for induction, autologous stem cell transplantation (ASCT) in eligible patients and maintenance therapy.1 Achievement of complete response (CR) post transplant is associated with improved PFS and overall survival (OS).2, 3 Factors—for example, baseline ISS stage III or revised ISS III (including high-risk cytogenetics and high serum LDH),4 use of more than two lines of induction therapy2, 3 are associated with inferior outcome. 5–20% of myeloma patients at diagnosis have extra-medullary disease (EMD) involving soft tissue and/or viscera.5, 6, 7 Such patients have inferior outcome with induction therapy.7 Limited data exist on their outcome following ASCT.8, 9

We have analyzed data on 271 consecutive ASCT recipients for MM; 44 (16.2%) had EMD. Patients median age was 52 years ranging from 29 to 68 years, 191 were males. Twenty-eight percent of patients had ISS stage III at diagnosis. Sites of EMD were soft tissue mass around axial skelton (n=30), pleural effusion, lymph node enlargement or visceral involvement (n=8) and six patients had both. Diagnosis of EMD was confirmed on imaging (MRI/PET scan), and/or biopsy/cytology. Pre-transplant, 27 of 44 patients (61.4%) had received induction using novel agents. The median interval from diagnosis to transplant was 11.5 months (range 2–74.5 months). High dose melphalan 200 mg/m2 was used for conditioning.3 Response to transplant was assessed according to the EBMT criteria (Table 1). Post transplant, patients with EMD took longer to platelet transfusion independence (days to achieve platelet counts ⩾20 000/cmm); 36.3 vs 17.3 days, P<0.001 and required higher mean single donor platelets units; 3.45 vs 3.41, P<0.04). Mean CD34+ cell count, time to achieve absolute neutrophil count ⩾500/cmm, days of fever, antibiotics and hospitalization, use of growth factors were not significantly different in EMD vs remaining patients (Supplementary Table 1). 16 of 44 patients (36.4%) achieved CR post ASCT compared to 142 (89.9%) among those without EMD, P<0.002. Within EMD group, CR rates were superior for those who received novel agents vs VAD (vincristine, doxorubicin and dexamethasone) and alkylating agents; 12/23 vs 2/21, P<0.02. For patients who received novel agents-response rate (⩾PR) was similar for thalidomide (n=10), lenalidomide (n=6) and bortezomib (n=5) and 3 drug (n=2) based regimen. Serum albumin (⩾3.5 G/dL) (P<0.03), pre-transplant chemosensitive disease (P<0.01), induction with novel agents (P<0.02), use of one regimen for induction (P<0.001) were associated with higher probability of achieving CR (Supplementary Table 2). Median OS for patients with EMD is 32 months (95% CI 17.8–46.2) vs 100.0 months (95% CI 79.8–120.2) for those without EMD, P<0.001 (Supplementary Figure 1). Corresponding median PFS is 18 months (95% CI 11.5–24.5) vs 44 months (95% CI 34.0–54.0), P<0.001 (Supplementary Figure 2). For OS—predictive factors were aged ⩽52 years, interval from diagnosis to transplant ⩽12 months, ISS stage I and II, DSS stage ⩽IIIA, serum albumin ⩾3.5 G/dL, BM plasma cells ⩽40%, induction with novel agents, use of one induction regimen, and achievement of CR post transplant. For PFS—serum albumin ⩾3.5 G/dL, BM plasma cells ⩽40%, induction with novel agents, one induction regimen and CR post transplant were positive predictors. (Table 2). On multivariate analysis—DSS stage ⩽IIIA and achievement of CR post transplant were predictors of OS. For PFS- ISS I and II, DSS ⩽IIIA, and achievement of CR post transplant were important predictors.

Table 1 Patients characteristics
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Table 2 Predictors of overall and progression-free survival: univariate analysis
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Authors and Affiliations

  1. Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

    L Kumar, R Gogi, A K Patel, A Mookerjee, R K Sahoo, P S Malik & A Sharma

  2. Department of Radio-diagnosis, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

    S Thulkar

  3. Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India

    R Kumar

  4. Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

    A Biswas

  5. Department of Laboratory Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

    O D Sharma & R Gupta

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Correspondence to L Kumar.

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Kumar, L., Gogi, R., Patel, A. et al. Multiple myeloma with extramedullary disease: impact of autologous stem cell transplantation on outcome. Bone Marrow Transplant 52, 1473–1475 (2017). https://doi.org/10.1038/bmt.2017.165

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